Dose aspects of radiation therapy planning and treatment

ABSTRACT

Radiation treatment planning includes accessing values of parameters such as a number of beams to be directed into sub-volumes in a target, beam directions, and beam energies. Information that specifies limits for the radiation treatment plan are accessed. The limits include a limit on irradiation time for each sub-volume outside the target. Other limits can include a limit on irradiation time for each sub-volume in the target, a limit on dose rate for each sub-volume in the target, and a limit on dose rate for each sub-volume outside the target. The values of the parameters are adjusted until the irradiation time for each sub-volume outside the target satisfies the maximum limit on irradiation time.

RELATED U.S. APPLICATIONS

This application is a continuation of the application with Ser. No.15/657,094, entitled “Dose Aspects of Radiation Therapy Planning andTreatment,” by R. Vanderstraeten et al., filed Jul. 21, 2017, now U.S.Pat. No. 10,092,774, and hereby incorporated by reference in itsentirety.

This application is related to U.S. application Ser. No. 15/657,052, byR. Vanderstraeten et al., entitled “Geometric Aspects of RadiationTherapy Planning and Treatment,” filed Jul. 21, 2017, now U.S. Pat. No.10,549,117, and hereby incorporated by reference in its entirety.

BACKGROUND

The use of radiation therapy to treat cancer is well known. Typically,radiation therapy involves directing a beam of high energy proton,photon, ion, or electron radiation (“therapeutic radiation”) into atarget or target volume (e.g., a tumor or lesion).

Before a patient is treated with radiation, a treatment plan specific tothat patient is developed. The plan defines various aspects of thetherapy using simulations and optimizations based on past experiences.In general, the purpose of the treatment plan is to deliver sufficientradiation to the target while minimizing exposure of surrounding normal,healthy tissue to the radiation.

The planner's goal is to find a solution that is optimal with respect tomultiple clinical goals that may be contradictory in the sense that animprovement toward one goal may have a detrimental effect on reachinganother goal. For example, a treatment plan that spares the liver fromreceiving a dose of radiation may result in the stomach receiving toomuch radiation. These types of tradeoffs lead to an iterative process inwhich the planner creates different plans to find the one plan that isbest suited to achieving the desired outcome.

A recent radiobiology study has demonstrated the effectiveness ofdelivering an entire, relatively high therapeutic radiation dose to atarget within a single, short period of time. This type of treatment isreferred to generally herein as FLASH radiation therapy (FLASH RT).Evidence to date suggests that FLASH RT advantageously spares normal,healthy tissue from damage when that tissue is exposed to only a singleirradiation for only a very short period of time. FLASH RT thusintroduces important constraints that are not considered in or achievedwith conventional radiation treatment planning.

SUMMARY

In intensity modulated radiation therapy (IMRT) such as intensitymodulated particle therapy (IMPT), beam intensity is varied across eachtreatment region (target) in a patient. Depending on the treatmentmodality, the degrees of freedom available for intensity modulationinclude beam shaping (collimation), beam weighting (spot scanning), andangle of incidence (which may be referred to as beam geometry). Thesedegrees of freedom lead to an effectively infinite number of potentialtreatment plans, and therefore consistently and efficiently generatingand evaluating high-quality treatment plans is beyond the capability ofa human and relies on the use of a computing system, particularlyconsidering the time constraints associated with the use of radiationtherapy to treat ailments like cancer, as well as the large number ofpatients that are undergoing or need to undergo radiation therapy duringany given time period.

Embodiments according to the present invention provide an improvedmethod of radiation treatment planning, and improved radiation treatmentbased on such planning, for FLASH radiation therapy (FLASH RT). Inembodiments, values of parameters such as a number of beams to bedirected into and across sub-volumes in a target, directions of thebeams (e.g., gantry angles relative to the patient or target, or nozzledirections relative to the patient or target), and beam energies for thebeams are accessed. The directions are determined such that an amount ofoverlap of the beams' paths outside the target is minimized or such thatthe paths of the beams do not overlap at all outside the target. Thebeams may or may not overlap within the target. The beams can be protonbeams, electron beams, photon beams, ion beams, or atom nuclei beams(e.g., carbon, helium, and lithium).

In embodiments, radiation treatment planning includes accessing valuesof parameters such as a number of beams to be directed into sub-volumesin a target, beam directions, and beam energies. Information thatspecifies limits for the radiation treatment plan is accessed. Inembodiments, the limits are based on a dose threshold, and include amaximum limit on irradiation time for each sub-volume outside thetarget. The dose threshold may be dependent on tissue type. Other limitscan include a maximum limit on irradiation time for each sub-volume inthe target, a minimum limit on dose rate for each sub-volume in thetarget, and a minimum limit on dose rate for each sub-volume outside thetarget. In embodiments, the values of the parameters are adjusted untilthe irradiation time for each sub-volume outside the target satisfiesthe maximum limit on irradiation time.

In embodiments, the portion of each beam within the target isrepresented as a respective set of longitudinal beam regions. Each beamregion in each set has a value corresponding to a calculated amount ofdose to be delivered by the beam region. For proton beams or ion beamsthat have a Bragg peak, the value assigned to the beam region thatcorresponds to the Bragg peak of the beam is greater than other valuesassigned to other beam regions. If two or more beams overlap within thetarget, then one or more sub-volumes within the target will receivedoses from more than one beam. For each sub-volume in the target, thevalues assigned to the beam regions that overlap in the sub-volume areadded together to determine a total value for the sub-volume; if onlyone beam region reaches a particular sub-volume, then the total value isthe value for that beam region. The parameters that affect thecalculated amounts of dose to be delivered by the beam regions areadjusted until the total values for the sub-volumes are within aspecified range of each other or are the same, thereby indicating thatthe dose to be delivered across the target is satisfactorily uniform.

In embodiments, a maximum energy for each beam is specified, and anenergy for each of the beam segments in the beam is determined as apercentage (100 percent or less) or equivalent fraction of that beam'smaximum energy. In embodiments, beams that have paths that overlapanother beam path outside the target are identified and the beamintensities for the beam segments of those beams are reduced in the dosecalculations. In one or more of these embodiments, the beam intensitiesfor beam segments of an overlapping beam are weighted according to howmany other beams are overlapped by that beam.

In embodiments, when performing a dose calculation for a sub-volume thatis outside the target, a value for a dose calculation factor for theoutside-the-target sub-volume is accessed. The value for the dosecalculation factor is based on how many beams are received by theoutside-the-target sub-volume. The value of the dose calculation factoris applied to the dose calculated for the outside-the-target sub-volumeto account for the tissue-sparing effects of FLASH RT on normal tissue.

In embodiments, the number of times (how many times) each beam can beturned on is determined, and the amount of time (for how long) a beamcan be turned on each time the beam is turned on is also determined,such that the total amount of time that a beam is turned on does notexceed a maximum limit for that beam. In this manner, a total amount oftime each sub-volume outside the target is irradiated by one beam(turned on one or more times) or by multiple beams (each beam turned onone or more times) does not exceed a maximum limit and, therefore, atotal amount of dose delivered to each sub-volume outside the targetdoes not exceed a maximum limit.

In embodiments according to the invention, instead of the conventionalapproach of specifying a maximum dose rate and a minimum treatment timein the treatment plan, limits are specified for a maximum irradiationtime for each sub-volume in the target, a maximum irradiation time foreach sub-volume outside the target, a minimum dose rate for eachsub-volume in the target, and a minimum dose rate for each sub-volumeoutside the target. As noted above, FLASH RT entails delivering arelatively high radiation dose to a target within a short period oftime. For example, each beam can deliver at least four grays (Gy) inless than one second, and may deliver as much as 20 Gy or 50 Gy or morein less than one second. In embodiments, the dose threshold is dependenton tissue type.

Embodiments according to the invention improve radiation treatmentplanning and the treatment itself by expanding FLASH RT to a widervariety of treatment platforms and target sites (e.g., tumors).Treatment plans generated as described herein are superior for sparingnormal tissue from radiation in comparison to conventional techniquesfor FLASH dose rates and even non-FLASH dose rates by reducing, if notminimizing, the magnitude of the dose, and in some cases the integrateddose, to normal tissue (outside the target) by design. When used withFLASH dose rates, management of patient motion is simplified. Treatmentplanning, while still a complex task, is simplified relative toconventional planning.

In summary, embodiments according to this disclosure pertain togenerating and implementing a treatment plan that is the most effective(relative to other plans) and with the least (or most acceptable) sideeffects (e.g., the lowest dose outside of the region being treated).Thus, embodiments according to the invention improve the field ofradiation treatment planning specifically and the field of radiationtherapy in general. Embodiments according to the invention allow moreeffective treatment plans to be generated quickly. Also, embodimentsaccording to the invention help improve the functioning of computersbecause, for example, by reducing the complexity of generating treatmentplans, fewer computational resources are needed and consumed, meaningalso that computer resources are freed up to perform other tasks.

In addition to IMRT and IMPT, embodiments according to the invention canbe used in spatially fractionated radiation therapy including high-dosespatially fractionated grid radiation therapy and microbeam radiationtherapy.

These and other objects and advantages of embodiments according to thepresent invention will be recognized by one skilled in the art afterhaving read the following detailed description, which are illustrated inthe various drawing figures.

This summary is provided to introduce a selection of concepts that arefurther described below in the detailed description that follows. Thissummary is not intended to identify key features or essential featuresof the claimed subject matter, nor is it intended to be used to limitthe scope of the claimed subject matter.

BRIEF DESCRIPTION OF DRAWINGS

The accompanying drawings, which are incorporated in and form a part ofthis specification and in which like numerals depict like elements,illustrate embodiments of the present disclosure and, together with thedetailed description, serve to explain the principles of the disclosure.

FIG. 1 is a block diagram of an example of a computing system upon whichthe embodiments described herein may be implemented.

FIG. 2 is a block diagram illustrating an example of an automatedradiation therapy treatment planning system in embodiments according tothe present invention.

FIG. 3 illustrates a knowledge-based planning system in embodimentsaccording to the present invention.

FIG. 4A is a block diagram showing selected components of a radiationtherapy system upon which embodiments according to the present inventioncan be implemented.

FIG. 4B is a block diagram illustrating a non-coplanar arrangement of agantry and nozzle relative to a patient support device in embodimentsaccording to the invention.

FIG. 4C is a block diagram illustrating a coplanar arrangement of agantry and nozzle relative to a patient support device in embodimentsaccording to the invention.

FIG. 4D is a block diagram illustrating movement of a gantry and nozzlearound a patient support device in embodiments according to theinvention.

FIG. 5 is a flowchart of an example of computer-implemented operationsfor generating a radiation treatment plan in embodiments according tothe present invention.

FIG. 6A illustrates a perspective view of an example of a beam geometryin embodiments according to the invention.

FIG. 6B illustrates a cross-sectional view of an example of a beamgeometry in embodiments according to the invention.

FIG. 6C illustrates a perspective view of an example of a beam geometryin embodiments according to the invention.

FIG. 6D illustrates a cross-sectional view of an example of a beamgeometry in embodiments according to the invention.

FIG. 7A illustrates a beam's eye view of a beam in embodiments accordingto the invention.

FIG. 7B is a flowchart of an example of computer-implemented operationsfor weighting beam segments during radiation treatment planning inembodiments according to the present invention.

FIG. 7C is an example of a depth dose curve for a beam segment inembodiments according to the invention.

FIG. 7D illustrates a cross-sectional view of a target and a beamincluding beam segments in embodiments according to the invention.

FIG. 8A is an example of a depth dose curve for a beam in embodimentsaccording to the invention.

FIGS. 8B, 8C, and 8D illustrate beams in a portion of a target inembodiments according to the invention.

FIG. 9 is a flowchart of an example of computer-implemented operationsfor generating a radiation treatment plan in embodiments according tothe present invention.

FIGS. 10A and 10B are examples of dose thresholds in embodimentsaccording to the present invention.

FIG. 11 is a flowchart of an example of computer-implemented operationsfor radiation treatment planning in embodiments according to the presentinvention.

FIG. 12 is a flowchart of an example of computer-implemented operationsfor radiation treatment planning in embodiments according to the presentinvention.

FIG. 13 is a flowchart of an example of computer-implemented operationsfor calculating doses during radiation treatment planning in embodimentsaccording to the present invention.

DETAILED DESCRIPTION

Reference will now be made in detail to the various embodiments of thepresent disclosure, examples of which are illustrated in theaccompanying drawings. While described in conjunction with theseembodiments, it will be understood that they are not intended to limitthe disclosure to these embodiments. On the contrary, the disclosure isintended to cover alternatives, modifications and equivalents, which maybe included within the spirit and scope of the disclosure as defined bythe appended claims. Furthermore, in the following detailed descriptionof the present disclosure, numerous specific details are set forth inorder to provide a thorough understanding of the present disclosure.However, it will be understood that the present disclosure may bepracticed without these specific details. In other instances, well-knownmethods, procedures, components, and circuits have not been described indetail so as not to unnecessarily obscure aspects of the presentdisclosure.

Some portions of the detailed descriptions that follow are presented interms of procedures, logic blocks, processing, and other symbolicrepresentations of operations on data bits within a computer memory.These descriptions and representations are the means used by thoseskilled in the data processing arts to most effectively convey thesubstance of their work to others skilled in the art. In the presentapplication, a procedure, logic block, process, or the like, isconceived to be a self-consistent sequence of steps or instructionsleading to a desired result. The steps are those utilizing physicalmanipulations of physical quantities. Usually, although not necessarily,these quantities take the form of electrical or magnetic signals capableof being stored, transferred, combined, compared, and otherwisemanipulated in a computing system. It has proven convenient at times,principally for reasons of common usage, to refer to these signals astransactions, bits, values, elements, symbols, characters, samples,pixels, or the like.

It should be borne in mind, however, that all of these and similar termsare to be associated with the appropriate physical quantities and aremerely convenient labels applied to these quantities. Unlessspecifically stated otherwise as apparent from the followingdiscussions, it is appreciated that throughout the present disclosure,discussions utilizing terms such as “determining,” “accessing,”“directing,” “controlling,” “defining,” “arranging,” “generating,”“representing,” “applying,” “adding,” “multiplying,” “adjusting,”“calculating,” “predicting,” “weighting,” “assigning,” “using,”“identifying,” “reducing,” “downloading,” “reading,” “computing,”“storing,” or the like, refer to actions and processes (e.g., theflowcharts of FIGS. 5, 7B, 9, 11, 12, and 13) of a computing system orsimilar electronic computing device or processor (e.g., the computingsystem 100 of FIG. 1). The computing system or similar electroniccomputing device manipulates and transforms data represented as physical(electronic) quantities within the computing system memories, registersor other such information storage, transmission or display devices.Terms such as “dose” or “fluence” generally refer to a dose or fluencevalue; the use of such terms will be clear from the context of thesurrounding discussion.

Portions of the detailed description that follows are presented anddiscussed in terms of a method. Although steps and sequencing thereofare disclosed in figures herein (e.g., FIGS. 5, 7B, 9, 11, 12, and 13)describing the operations of this method, such steps and sequencing areexemplary. Embodiments are well suited to performing various other stepsor variations of the steps recited in the flowchart of the figureherein, and in a sequence other than that depicted and described herein.

Embodiments described herein may be discussed in the general context ofcomputer-executable instructions residing on some form ofcomputer-readable storage medium, such as program modules, executed byone or more computers or other devices. By way of example, and notlimitation, computer-readable storage media may comprise non-transitorycomputer storage media and communication media. Generally, programmodules include routines, programs, objects, components, datastructures, etc., that perform particular tasks or implement particularabstract data types. The functionality of the program modules may becombined or distributed as desired in various embodiments.

Computer storage media includes volatile and nonvolatile, removable andnon-removable media implemented in any method or technology for storageof information such as computer-readable instructions, data structures,program modules or other data. Computer storage media includes, but isnot limited to, random access memory (RAM), read only memory (ROM),electrically erasable programmable ROM (EEPROM), flash memory or othermemory technology, compact disk ROM (CD-ROM), digital versatile disks(DVDs) or other optical storage, magnetic cassettes, magnetic tape,magnetic disk storage or other magnetic storage devices, or any othermedium that can be used to store the desired information and that canaccessed to retrieve that information.

Communication media can embody computer-executable instructions, datastructures, and program modules, and includes any information deliverymedia. By way of example, and not limitation, communication mediaincludes wired media such as a wired network or direct-wired connection,and wireless media such as acoustic, radio frequency (RF), infrared andother wireless media. Combinations of any of the above can also beincluded within the scope of computer-readable media.

FIG. 1 shows a block diagram of an example of a computing system 100upon which the embodiments described herein may be implemented. In itsmost basic configuration, the system 100 includes at least oneprocessing unit 102 and memory 104. This most basic configuration isillustrated in FIG. 1 by dashed line 106. The system 100 may also haveadditional features and/or functionality. For example, the system 100may also include additional storage (removable and/or non-removable)including, but not limited to, magnetic or optical disks or tape. Suchadditional storage is illustrated in FIG. 1 by removable storage 108 andnon-removable storage 120. The system 100 may also containcommunications connection(s) 122 that allow the device to communicatewith other devices, e.g., in a networked environment using logicalconnections to one or more remote computers.

The system 100 also includes input device(s) 124 such as keyboard,mouse, pen, voice input device, touch input device, etc. Outputdevice(s) 126 such as a display device, speakers, printer, etc., arealso included.

In the example of FIG. 1, the memory 104 includes computer-readableinstructions, data structures, program modules, and the like associatedwith an “optimizer” model 150. However, the optimizer model 150 mayinstead reside in any one of the computer storage media used by thesystem 100, or may be distributed over some combination of the computerstorage media, or may be distributed over some combination of networkedcomputers. The functionality of the optimizer model 150 is describedbelow.

FIG. 2 is a block diagram illustrating an example of an automatedradiation therapy treatment planning system 200 in embodiments accordingto the present invention. The system 200 includes an input interface 210to receive patient-specific information (data) 201, a data processingcomponent 220 that implements the optimizer model 150, and an outputinterface 230. The system 200 in whole or in part may be implemented asa software program, hardware logic, or a combination thereof on/usingthe computing system 100 (FIG. 1).

In the example of FIG. 2, the patient-specific information is providedto and processed by the optimizer model 150. The optimizer model 150yields a prediction result. A treatment plan based on the predictionresult can then be generated.

FIG. 3 illustrates a knowledge-based planning system 300 in embodimentsaccording to the present invention. In the example of FIG. 3, the system300 includes a knowledge base 302 and a treatment planning tool set 310.The knowledge base 302 includes patient records 304 (e.g., radiationtreatment plans), treatment types 306, and statistical models 308. Thetreatment planning tool set 310 in the example of FIG. 3 includes acurrent patient record 312, a treatment type 314, a medical imageprocessing module 316, the optimizer model (module) 150, a dosedistribution module 320, and a final radiation treatment plan 322.

The treatment planning tool set 310 searches through the knowledge base302 (through the patient records 304) for prior patient records that aresimilar to the current patient record 312. The statistical models 308can be used to compare the predicted results for the current patientrecord 312 to a statistical patient. Using the current patient record312, a selected treatment type 306, and selected statistical models 308,the tool set 310 generates a radiation treatment plan 322.

More specifically, based on past clinical experience, when a patientpresents with a particular diagnosis, stage, age, weight, sex,co-morbidities, etc., there can be a treatment type that is used mostoften. By selecting the treatment type that the planner has used in thepast for similar patients, a first-step treatment type 314 can bechosen. The medical image processing module 316 provides automaticcontouring and automatic segmentation of two-dimensional cross-sectionalslides (e.g., from computed tomography or magnetic resonance imaging) toform a three-dimensional (3D) image using the medical images in thecurrent patient record 312. Dose distribution maps are calculated by thedose distribution module 320, which may utilize the optimizer model 150.

In embodiments according to the present invention, the optimizer model150 uses a dose prediction model to help shape the dose distribution.The optimizer model 150 can provide, for example, a 3D dosedistribution, fluences, and associated dose-volume histograms for thecurrent patient.

FIG. 4A is a block diagram showing selected components of a radiationtherapy system 400 upon which embodiments according to the presentinvention can be implemented. In the example of FIG. 4A, the system 400includes a beam system 404 and a nozzle 406.

The beam system 404 generates and transports a beam 401 to the nozzle406. The beam 401 can be a proton beam, electron beam, photon beam, ionbeam, or atom nuclei beam (e.g., carbon, helium, and lithium). Inembodiments, depending on the type of beam, the beam system 404 includescomponents that direct (e.g., bend, steer, or guide) the beam system ina direction toward and into the nozzle 406. In embodiments, theradiation therapy system may include one or more multileaf collimators(MLCs); each MLC leaf can be independently moved back-and-forth by thecontrol system 410 to dynamically shape an aperture through which thebeam can pass, to block or not block portions of the beam and therebycontrol beam shape and exposure time. The beam system 404 may alsoinclude components that are used to adjust (e.g., reduce) the beamenergy entering the nozzle 406.

The nozzle 406 is used to aim the beam toward various locations (atarget) within an object (e.g., a patient) supported on the patientsupport device 408 (e.g., a chair or table) in a treatment room. Atarget may be an organ, a portion of an organ (e.g., a volume or regionwithin the organ), a tumor, diseased tissue, or a patient outline.

The nozzle 406 may be mounted on or a part of a gantry (FIGS. 4B, 4C,and 4D) that can be moved relative to the patient support device 408,which may also be moveable. In embodiments, the beam system 404 is alsomounted on or is a part of the gantry; in another embodiment, the beamsystem is separate from (but in communication with) the gantry.

The control system 410 of FIG. 4A receives and implements a prescribedtreatment plan. In embodiments, the control system 410 includes acomputer system having a processor, memory, an input device (e.g., akeyboard), and perhaps a display in well-known fashion. The controlsystem 410 can receive data regarding operation of the system 400. Thecontrol system 410 can control parameters of the beam system 404, nozzle406, and patient support device 408, including parameters such as theenergy, intensity, direction, size, and/or shape of the beam, accordingto data it receives and according to the prescribed treatment plan.

As noted above, the beam entering the nozzle 406 has a specified energy.Thus, in embodiments according to the present disclosure, the nozzle 406includes one or more components that affect (e.g., decrease, modulate)the energy of the beam. The term “beam energy adjuster” is used hereinas a general term for a component or components that affect the energyof the beam, in order to control the range of the beam (e.g., the extentthat the beam penetrates into a target), to control the dose deliveredby the beam, and/or to control the depth dose curve of the beam,depending on the type of beam. For example, for a proton beam or an ionbeam that has a Bragg peak, the beam energy adjuster can control thelocation of the Bragg peak in the target. In various embodiments, thebeam energy adjuster 407 includes a range modulator, a range shifter, orboth a range modulator and a range shifter. That is, when the term “beamenergy adjuster” is used, then the element being discussed may be arange modulator, a range shifter, or both a range modulator and a rangeshifter. Examples of a beam energy adjuster for proton beams and ionbeams are disclosed in the co-pending patent application, U.S.application Ser. No. 15/089,330, entitled “Radiation Therapy Systems andMethods” (as-filed); however, the invention is not so limited.

FIG. 4B is a block diagram illustrating a non-coplanar arrangement of agantry 420 and nozzle 406 relative to a patient support device 408 inembodiments according to the invention. FIG. 4C is a block diagramillustrating a coplanar arrangement of a gantry 420 and nozzle 406relative to a patient support device 408 and also illustrating movementof the gantry and nozzle around the patient support device inembodiments according to the invention. FIG. 4D is a block diagramillustrating movement of the gantry 420 and nozzle 406 around thepatient support device 408 in embodiments according to the invention.This movement can occur in either the non-coplanar arrangement or thecoplanar arrangement.

FIG. 5 is a flowchart 500 of an example of computer-implementedoperations for generating a radiation treatment plan in embodimentsaccording to the present invention. The flowchart 500 can be implementedas computer-executable instructions (e.g., the optimizer model 150 ofFIG. 1) residing on some form of computer-readable storage medium (e.g.,using the computing system 100 of FIG. 1).

In intensity modulated radiation therapy (IMRT) such as intensitymodulated particle therapy (IMPT), beam intensity is varied across eachtreatment region (target) in a patient. Depending on the treatmentmodality, the degrees of freedom available for intensity modulationinclude beam shaping (collimation), beam weighting (spot scanning), andangle of incidence (which may be referred to as beam geometry). Thesedegrees of freedom lead to an effectively infinite number of potentialtreatment plans, and therefore consistently and efficiently generatingand evaluating high-quality treatment plans is beyond the capability ofa human and relies on the use of a computing system, particularlyconsidering the time constraints associated with the use of radiationtherapy to treat ailments like cancer, as well as the large number ofpatients that are undergoing or need to undergo radiation therapy duringany given time period.

In block 502 of FIG. 5, a prescribed dose to be delivered into andacross the target is determined. Each portion of the target can berepresented by at least one 3D element known as a voxel; a portion mayinclude more than one voxel. A portion of a target or a voxel may alsobe referred to herein as a sub-volume; a sub-volume may include one ormore portions or one or more voxels. As will be described in detailbelow, each portion or voxel may receive radiation from one or morebeams delivered from different directions. The prescribed dose defines,for example, a dose value, or a minimum dose value and a maximum dosevalue, for each portion or voxel of the target. In embodiments, theprescribed dose is the same for all portions (sub-volumes or voxels) ofthe target, such that a uniform dose is prescribed for the entiretarget.

In block 504, directions (e.g., gantry angles relative to the patient ortarget, or nozzle directions relative to the patient or target) fordelivering beams into the target are determined. The beams can be protonbeams, electron beams, photon beams, ion beams, or atom nuclei beams.The operation of determining beam directions can include determining thenumber of beams (the number of directions from which beams are to bedelivered). The beams' paths may or may not overlap within the target,and may or may not overlap outside the target. In general, whengenerating the radiation treatment plan, one goal is to determine beampaths that minimize the irradiation time of each sub-volume or voxel ofthe tissue outside the target. Ideally, each sub-volume or voxel outsidethe target is intersected, at most, by only a single beam. If someoverlap between beam paths is permitted, then ideally each sub-volume orvoxel outside the target is intersected by not more than two beams, withmost intersected by only a single beam. In embodiments, as one means ofachieving the aforementioned goal, the beam directions are determinedsuch that the total amount of overlap between the beams' paths isminimized outside the target. In one such embodiment, the directions aredetermined such that the paths of the beams overlap within the targetand such that the total amount of overlap of the beams' paths outsidethe target is less than the total amount of the overlap of the beams'paths within the target. In another such embodiment, the directions aredetermined so that the paths of the beams do not overlap at all outsidethe target. The beams' paths can lie within the same plane, or they canbe in different planes. Additional information is provided inconjunction with FIGS. 6A, 6B, 6C, and 6D.

Any number of other factors may be considered when determining the beamdirections. These factors may include the shape and size (e.g., height Hand width W, or diameter) of the beam in the beam's eye view (see FIG.7A). These factors may also include, for example, the amount or type ofhealthy tissue that a beam will be traveling through. That is, one beamdirection may be more favorable than another if it travels a shorterdistance through healthy tissue or avoids passing through a vital organand may be weighted accordingly.

In block 506 of FIG. 5, a beam energy or intensity is determined foreach of the directions (for each of the beams). The beam energy orintensity for each direction is determined such that the predicted orcalculated cumulative doses (e.g., doses calculated using the optimizermodel 150 of FIG. 1) at locations inside the target satisfy theprescribed dose as defined in block 502. As noted, beam paths may or maynot overlap in the target; if the beams' paths overlap in the target,then the beam energy or intensity for each direction is determined suchthat the predicted or calculated cumulative doses (e.g., dosescalculated using the optimizer model 150 of FIG. 1) at locations insidethe target where the beams' paths overlap satisfy the prescribed dose asdefined in block 502. In embodiments, a beam includes a number of beamsegments or beamlets. In one or more such embodiments, a maximum energy(e.g., 80 MeV) for the beam is specified, and an energy for each of thebeam segments is determined as a percentage (100 percent or less) orequivalent fraction of the maximum beam energy. In general, beams canhave the same energy or different energies, and each beam can have arange of energies. Thus, different energies or intensities can bedelivered in different directions, and different energies or intensitiescan be delivered in each direction. Additional information is providedin conjunction with FIGS. 7A, 7B, 7C, and 7D.

While the operations in blocks 502, 504, and 506 of FIG. 5 are presentedas occurring in series and in a certain order, the present invention isnot so limited. The operations may be performed in a different orderand/or in parallel, and they may also be performed in an iterativemanner, as the number of beams (and accordingly, the number ofdirections), the beam directions, and the beam energies or intensities(and/or beam segment energies or intensities) used to deliver theprescribed dose are interrelated. As noted above, because of thedifferent parameters that need to be considered, the range of values forthose parameters, the interrelationship of those parameters, the needfor treatment plans to be effective yet minimize risk to the patient,and the need to generate high-quality treatment plans quickly, the useof the optimizer model 150 executing consistently on the computingsystem 100 (FIG. 1) for radiation treatment planning as disclosed hereinis important.

The discussion to follow refers to beams, targets, doses, and otherelements or values. The discussion below is in the context of modeledelements and calculated values in the treatment planning tool set 310and the optimizer model 150 (FIG. 3), unless otherwise noted or madeclear in the discussion.

FIG. 6A illustrates a perspective view of an example of a beam geometryin embodiments according to the invention. In the example of FIG. 6A,the beams (exemplified by beam 602) are in the same plane. The beams canbe proton beams, electron beams, photon beams, ion beams, or atom nucleibeams. Each beam can deliver a relatively high dose in a relativelyshort period of time. For example, in embodiments, each beam can deliverdoses sufficient for FLASH RT (e.g., at least four (4) grays (Gy) inless than one second, and as much as 20 Gy or 50 Gy or more in less thanone second). In embodiments, the range is 0.01-500 Gy. As describedherein, each beam can include one or more beam segments or beam lets. Inthis example, the beams' paths overlap only within the target 604, anddo not overlap outside the target in the surrounding tissue 606.

In the example of FIG. 6A, the beam 602 (for example) is illustrated aspassing completely through the target 604. For beams that have a Braggpeak (e.g., proton beams and ion beams), the ranges of the beams can becontrolled so that the beam does not pass completely through the target,as will be described further below.

Although multiple beams are shown in FIG. 6A, this does not mean thatall beams are necessarily delivered at the same time or in overlappingtime periods, although they can be. The number of beams delivered at anyone time depends on the number of gantries or nozzles in the radiationtreatment system (e.g., the radiation treatment system 400 of FIG. 4A)and on the treatment plan.

FIG. 6B illustrates a cross-sectional view of an example of a beamgeometry in embodiments according to the invention. In this example, thebeams (exemplified by beams 605 and 606) overlap only within the targetand are in the same plane. The figure depicts the beams in overlappingfashion to demonstrate that each portion of the target 604 receives adose of radiation. The beams can be proton beams, electron beams, photonbeams, ion beams, or atom nuclei beams. In the example of FIG. 6B, thebeams are illustrated as not extending beyond the distal edge of thetarget 604 (as would be the case for proton or ion beams, for example);however, the invention is not so limited. Each beam can deliver arelatively high dose in a relatively short period of time. For example,each beam can deliver doses sufficient for FLASH RT.

As will be discussed further in conjunction with FIG. 7C, forimplementations in which the beams have a Bragg peak, such as a protonbeam or an ion beam, the dose delivered by a beam (or beam segment) isnot necessarily uniform along the entire length of the beam path throughthe target 604. Thus, for example, for a proton or ion beam, the dosedelivered by the beam 605 at the proximal portion (or edge) 608 of thetarget 604 may be different from (e.g., less than) the dose delivered bythat beam at the distal portion (or edge) 610 of the target (here,proximal and distal are with reference to the source of the beam 605).The same can be said for each proton or ion beam.

The dose delivered to each portion of the target 604 is cumulative,based on the number of beams that are delivered to and through thatportion. For example, the portions of the target 604 covered by thebeams 605 and 606 receive a total dose that is the sum of the dosedelivered by the beam 605 and the dose delivered by the beam 606. Inembodiments, the energies of the beams (beam segments) are accuratelydetermined so that, even though the dose along each beam (or beamsegment) is not uniform, a uniform cumulative dose distribution isachieved within and across the target 604.

FIG. 6C illustrates a perspective view of an example of a beam geometryin embodiments according to the invention. In the example of FIG. 6C,the beams (exemplified by beam 612) are in different planes. Asdescribed herein, each beam can include one or more beam segments orbeam lets. In this example, the beams' paths overlap only within thetarget 604, and do not overlap outside the target in the surroundingtissue 606. Although multiple beams are shown in the figure, all beamsare not necessarily delivered at the same time or in overlapping timeperiods as mentioned above. The beams can be proton beams, electronbeams, photon beams, ion beams, or atom nuclei beams. Each beam candeliver a relatively high dose in a relatively short period of time. Forexample, each beam can deliver doses sufficient for FLASH RT.

FIG. 6D illustrates a cross-sectional view of an example of a beamgeometry in embodiments according to the invention. In this example, thebeams (exemplified by beams 621, 622, and 623) overlap only within thetarget and are in the same plane. While three beams are illustrated, theinvention is not so limited. As described herein, each beam can includeone or more beam segments or beamlets. In this example, the beams' pathsoverlap only within the target 604, and do not overlap outside thetarget in the surrounding tissue 606. Although multiple beams are shownin the figure, all beams are not necessarily delivered at the same timeor in overlapping time periods as mentioned above. The beams can beproton beams, electron beams, photon beams, ion beams, or atom nucleibeams. Each beam can deliver a relatively high dose in a relativelyshort period of time. For example, each beam can deliver dosessufficient for FLASH RT.

In the example of FIG. 6D, the beams 621, 622, and 623 intersect at thesub-volume 630, other sub-volumes in the target 604 receive doses fromtwo of the beams, other sub-volumes in the target receive doses fromonly one of the beams, and yet other sub-volumes do not receive a dose.The directions and/or numbers of beam can be varied over a number oftreatment sessions (that is, fractionated in time) so that a uniformdose is delivered across the target.

As mentioned above, for implementations that use proton beams or ionbeams, the dose delivered by each beam at the respective proximalportion (or edge) of the target 604 may be different from (e.g., lessthan) the dose delivered by that beam at the respective distal portion(or edge) of the target (as before, proximal and distal are withreference to the source of the beam).

The dose delivered to each portion of the target 604 is cumulative,based on the number of beams that are delivered to and through thatportion. Not all beams are depicted in the figures for simplicity; ingeneral, the number of beams is sufficient to achieve a uniformcumulative dose distribution within the target 604.

In general, the surface of a target can be viewed as having a number ofdiscrete facets. From this perspective, for beams other than photonbeams, each incident beam is orthogonal to each facet such that thebeams do not overlap outside the target. In the case of photon beams,each incident beam is parallel to the facet and does not overlap otherbeams outside the target.

FIG. 7A illustrates a beam's eye view (BEV) of a beam 702 in embodimentsaccording to the invention. That is, FIG. 7A illustrates a cross-sectionof a beam. The beams of FIGS. 6A, 6B, 6C, and 6D are examples of thebeam 702. The beam 702 is illustrated as being rectangular in shapehaving a height H and width W. However, the invention is not so limited,and the beam 702 can have virtually any regular or irregularcross-sectional (e.g., BEV) shape. For example, the shape of the beam702 can be defined using an MLC that blocks a portion or portions of thebeam. Different beams can have different shapes.

In the FIG. 7A embodiment, the beam 702 includes a number of beamsegments or beam lets (that also may be referred to as spots)exemplified by beam segments 704, 706, and 708. A maximum energy (e.g.,80 MeV) is specified for the beam 702, and an energy level is definedfor each of the beam segments as a percentage or fraction of the maximumenergy. In essence, each of the beam segments is weighted in terms ofits energy level; some beam segments are weighted to have a higherenergy level than other beam segments. By weighting the energy per beamsegment, in effect the intensity of each beam segment is also weighted.The energy per beam segment is defined so that the beam segment willdeliver a fraction of the prescribed dose such that, in combination withthe other beam segments in the beam, and in combination with the otherbeams (and beam segments), a uniform (homogeneous) cumulative dose thatsatisfies the prescribed dose will be delivered within and across thevolume of the target. The defined energy level or intensity can berealized for each beam segment using the beam energy adjuster 407 ofFIG. 4A.

Each beam segment can deliver a relatively high dose in a relativelyshort period of time. For example, each beam segment can deliver atleast 4 Gy in less than one second, and may deliver as much as 20 Gy or50 Gy or more in less than one second. The energy or intensity of eachbeam segment can be controlled using the beam energy adjuster 407 ofFIG. 4A so that the beam segment has sufficient energy to reach thedistal edge of the target.

In operation, in embodiments, the beam segments are deliveredsequentially. For example, the beam segment 704 is delivered to thetarget (turned on) and then turned off, then the beam segment 706 isturned on then off, then the beam segment 708 is turned on then off, andso on. Each beam segment may be turned on for only a fraction of asecond (on the order of milliseconds).

FIG. 7B is a flowchart 750 of an example of computer-implementedoperations for weighting beam segments during radiation treatmentplanning in embodiments according to the present invention. Theflowchart 750 can be implemented as computer-executable instructions(e.g., the optimizer model 150 of FIG. 3) residing on some form ofcomputer-readable storage medium (e.g., using the computing system 100of FIG. 1).

Embodiments according to the invention introduce an additional parameterduring weighting of the beam segments in the beams (also referred to asspot weighting), depending on whether a beam overlaps another beamoutside the target.

In block 752 of FIG. 7B, a prescribed dose to be delivered into andacross a target is determined. The prescribed dose can be generatedusing the system 300 of FIG. 3.

In block 754 of FIG. 7B, values of parameters such as the number ofbeams to be directed into sub-volumes in the target, directions of thebeams, and beam energies are accessed. As described above, the beams'paths overlap inside the target. These parameter values can be generatedusing the system 300 of FIG. 3.

In block 756 of FIG. 7B, any beams that overlap outside the target areidentified.

In block 758, for each beam, a maximum beam energy for the beam isdetermined.

In block 760, for each beam, beam energies for the beam segments aredetermined as a percentage of the maximum beam energy for the beam.

In block 762, for each overlapping beam identified in block 756, thebeam energies for the beam segments of those beams are reduced by arespective factor. The factor can be increased (to increase the amountof reduction) for a beam that intersects more than one other beam. Inother words, the penalty is greater if normal (healthy) tissue is hit bymore than one beam. The factors applied to the beam energies for thesebeam segments are determined such that the cumulative dose delivered tothe target satisfies the prescribed dose. In this manner, the beamenergies or intensities and the associated doses for beams that overlapoutside the target are reduced while still allowing the prescribed doseto be delivered to the target.

FIG. 7C is an example of a depth dose curve for a beam segment for abeam such as a proton beam or an ion beam that has a Bragg peak inembodiments according to the invention. The example of FIG. 7C showscalculated dose level as a function of depth in the target (distancefrom the beam source) for the beam 702 or for any of the beam segmentsin the beam. The energy level or intensity of each beam segment can becontrolled using the beam energy adjuster 407 (FIG. 4A) such that theBragg peak is in the portion at (adjacent to or near) the distal edge ofthe target as shown in FIG. 7C.

With reference back to FIG. 6B, it can be seen (or deduced) that greaterportions of each beam overlap toward the center of the target 604 thanat the edges of the target, and more beams overlap at or near the centerof the target 604 than at the edges of the target. For example, thebeams 602 and 603 do not overlap at the proximal edge 608 of the target604, overlap more toward the center of the target, overlap completely ator near the center of the target, and overlap partially past the centerand at the distal edge 610. All beams overlap at the center of thetarget 604, but all beams do not overlap at the edges of the target. Asmentioned previously herein, the dose contributed by each beam iscumulative, and the target 604 can be represented by the 3D elementsknown as voxels or sub-volumes. Each voxel or sub-volume will receiveradiation from one or more beam segments delivered from differentdirections. The total dose for a voxel is the sum of the doses deliveredby each beam segment received by the voxel. By shaping the beam segmentsas shown in the example of FIG. 7C for beams (e.g., proton beams and ionbeams) that have a Bragg peak, the portions or voxels or sub-volumes inthe target 604 that are traversed by fewer beams (beam segments) willreceive a larger dose per beam segment because the Bragg peaks of thosebeam segments coincide with the locations of thoseportions/voxels/sub-volumes, while the portions/voxels/sub-volumes inthe target that are traversed by more beams (beam segments) will receivea smaller dose per beam segment because the Bragg peaks of the latterbeam segments do not coincide with the locations of the latterportions/voxels. In other words, the Bragg peak of each beam is at thedistal edge of the target 604, where there is less overlap betweenbeams, and the dose per beam is less than the Bragg peak at locationsinside the target where there is more overlap between beams. In thismanner, for embodiments that use beams that have Bragg peaks, a uniformdose can be delivered within and across the target 604.

FIG. 7D illustrates a cross-sectional view of an irregularly shapedtarget 715 and a beam 720 that includes four beam segments 721, 722,723, and 724 in the longitudinal direction in embodiments according tothe invention. As described above, the energy of each of the beamsegments 721, 722, 723, and 724 can be individually defined andindependently controlled (e.g., using the beam energy adjuster 407 ofFIG. 4A) so that the beam segment has sufficient energy to reach thedistal edge of the target 715. In particular, for beams like protonbeams and ion beams that have Bragg peaks, the energy level of the beamsegments 721, 722, 723, and 724 can be independently controlled usingthe beam energy adjuster 407 such that the Bragg peak of each beamsegment is in the portion at (adjacent to or near) the distal edge ofthe target 715. In this manner, the range of the beam 720 can be shapedso that it follows the shape of the target 715 in the longitudinaldirection. The cross-sectional size (e.g., height and width or diameter)of each beam segment can be specified according to the complexity of theshape of the target 715. For example, if the target surface isrelatively uniform (e.g., flat), then the size of the beam segment canbe larger.

FIG. 8A is an example of a depth dose curve 802 for a beam 804 inembodiments according to the invention. The example of FIG. 8A showscalculated dose level as a function of depth in a target 806 (distancefrom the beam source) for the beam 804. In the example of FIG. 8A, thebeam 804 is a beam that has a Bragg peak (e.g., a proton beam or an ionbeam). FIG. 8B illustrates the beam 804 in a portion of the target 806in embodiments according to the invention. The following discussionpresents examples in the context of a beam; however, as described above,a beam can include beam segments, and the examples and discussion belowcan be readily extended to beam segments.

In the example of FIG. 8A, the depth dose curve 802 is divided into aset of regions 802 a, 802 b, 802 c, 802 d, and 802 e (802 a-e). Incorresponding fashion, the beam 804 is divided into a set oflongitudinal beam regions 804 a, 804 b, 804 c, 804 d, and 804 e (804a-e). The beam regions 804 a-e are aligned with the regions 802 a-e. Thewidths of the regions 802 a-e (and hence the lengths of the beam regions804 a-e) increase in size as the distance from the Bragg peak increasesbecause that is where the calculated dose is more homogeneous (where thedose curve is relatively flat). At and near the Bragg peak (e.g., theregions 802 c, 802 d, and 802 e), the regions are shorter/thinner.

Each of the beam regions 804 a-e is assigned a value xn (n=1, 2, . . . ,5 in the example) that corresponds to the calculated amount of dose forthe beam region. The region 804 a has a value of x1, the region 804 bhas a value x2, and so on. For example, the values xn may range from one(1) to 100. In embodiments, the values are generally proportional to theamount of calculated dose. In one or more such embodiments, the value x4for the beam region 804 d corresponding to the location 802 d of theBragg peak in the depth dose curve 802 is the largest value, greaterthan the other values assigned to the other beam regions in the beam804.

In FIG. 8B, the beam 804 is shown entering the target 806 from a certaindirection. If the beam 804 enters the target 806 from a differentdirection, then the values xn may be different. In other words, thevalues xn may be different depending on the gantry angle or beamdirection associated with the beam 806 even if the beam energy does notchange with angle or direction. In embodiments, values are assigned tothe beam regions 804 a-e depending on both the corresponding dose depthcurve 802 and the beam direction.

FIG. 8C shows a second beam 814 that passes through the target along thesame path as the beam 804 but in the opposite direction in embodimentsaccording to the invention. That is, paths of the beams 804 and 814overlap as in the example of FIG. 6B. In the present embodiments, thebeam 814 is a beam that has a Bragg peak (e.g., a proton beam or an ionbeam). The beams 804 and 814 are not necessarily delivered at the sametime although they can be.

Like the beam 804, the beam 814 is divided into a set of longitudinalbeam regions 814 a, 814 b, 814 c, 814 d, and 814 e (814 a-e) that arealigned with regions of a dose depth curve (not shown) for the beam 814.Each of the beam regions 814 a-e is assigned a value yn (n=1, 2, . . . ,5 in the example) that corresponds to the calculated amount of dose forthe beam region. The values yn may range from 1 to 100. In embodiments,the values at the radiation isocenter for the beams 804 and 814 are thesame.

When beams overlap in the target 806, the sub-volumes of the targettraversed by the beams receive a dose from each beam. In the examples ofFIGS. 8B and 8C, the cumulative dose for a sub-volume is represented byadding together the values of xn and yn corresponding to the regions ofthe beams 804 and 814 that traverse the sub-volume. FIG. 8D shows bothbeams 804 and 814 in overlapping fashion. In the example of FIG. 8D, thesub-volume 821 has a cumulative dose represented by x1+y5, thesub-volume 822 has a cumulative dose represented by x2+y5, thesub-volume 823 has a cumulative dose represented by x3+y5, thesub-volume 824 has a cumulative dose represented by x4+y5, thesub-volume 825 has a cumulative dose represented by x5+y5, thesub-volume 826 has a cumulative dose represented by x5+y4, thesub-volume 827 has a cumulative dose represented by x5+y3, thesub-volume 828 has a cumulative dose represented by x5+y2, and thesub-volume 829 has a cumulative dose represented by x5+y1.

As shown in FIG. 6B, a sub-volume can be traversed by more than twobeams, in which case the cumulative dose for the sub-volume isrepresented by adding the appropriate value for each beam that reachesthe sub-volume. That is, a total value is determined for each sub-volumein the target 806 by adding together the values for each beam region ofeach beam that reaches the sub-volume.

The optimizer model (FIG. 3) can adjust the parameters that affect thecalculated doses delivered to the target 806 to achieve a satisfactorilyuniform cumulative dose across the target 806. A satisfactorily uniformcumulative dose is indicated when all the total values per sub-volume inthe target 806 are the same or when the differences between the totalvalues per sub-volume satisfy a threshold value. The threshold value canbe, for example, a value that specifies the maximum amount of differencebetween total values that is permitted. That is, the parameters thataffect the calculated doses to be delivered by the beam regions areadjusted until the total values for the sub-volumes are all within aspecified range of each other or are the same, thereby indicating thatthe dose to be delivered across the target is satisfactorily uniform.

FIG. 9 is a flowchart 900 of an example of computer-implementedoperations for generating a radiation treatment plan in embodimentsaccording to the present invention. The flowchart 900 can be implementedas computer-executable instructions (e.g., the optimizer model 150 ofFIG. 3) residing on some form of computer-readable storage medium (e.g.,using the computing system 100 of FIG. 1).

In block 902 of FIG. 9, values of parameters such as a number of beamsto be directed into and across sub-volumes in a target, directions ofthe beams, and beam energies for the beams, are accessed. Theseparameter values can be generated using the system 300 of FIG. 3 and maybe stored in a memory of the computing system 100 of FIG. 1.

In block 904 of FIG. 9, each portion of the beams that is in the targetis represented as a respective set of longitudinal beam regions. See,for example, FIG. 8B and the discussion thereof.

In block 906, an amount of dose to be delivered by each of the beamregions is computed and a value is assigned to each beam regioncorresponding to the computed amount of dose for the beam region. See,for example, FIGS. 8B and 8C and the discussion thereof.

In block 908 of FIG. 9, for each sub-volume in the target, the value foreach beam region of each beam that reaches the sub-volume are addedtogether to generate a total value for the sub-volume. See, for example,FIG. 8D and the discussion thereof.

In block 910 of FIG. 9, the values of the parameters that affect thecalculated amounts of dose to be delivered by the beam regions areadjusted until differences between the total values for the sub-volumessatisfy a threshold value or are the same (in the latter case, thethreshold value is zero). That is, the values of the parameters areadjusted until the dose across the target is satisfactory (e.g., it isuniform or nearly uniform across the entire target).

In block 912, the adjusted parameter values are stored in memory of thecomputing system 100 (FIG. 1) as part of the radiation treatment plan322 (FIG. 3).

In embodiments according to the invention, a dose threshold is used tospecify limits for the radiation treatment plan. Examples of dosethresholds are presented in FIGS. 10A and 10B.

FIGS. 10A and 10B show normal (healthy) tissue sparing-dose as afunction of dose rate or irradiation time. In the example of FIG. 10A,the function is a step-wise function. In the example of FIG. 10B, thefunction is sigmoidal. Doses, dose rates, and irradiation times in FIGS.10A and 10B are only examples. Other functions can be used. The dosethreshold curves can be tissue-dependent. For instance, the dosethreshold curve for the lungs may be different from that for the brain.The appropriate dose threshold curve(s) can be utilized in theoptimization model 150 (FIG. 3) to establish dose limits for radiationtreatment planning. For example, the appropriate (e.g.,tissue-dependent) dose threshold curve can be used to determine beamdirections (gantry angles) and beam segment weights (FIG. 7A). That is,parameters that affect dose can be adjusted during radiation treatmentplanning so that the limits in the dose threshold curve are satisfied.

Dose limits can include, but are not limited to: a maximum limit onirradiation time for each sub-volume (voxel) in the target (e.g., foreach voxel of target tissue, treatment time less than x1 seconds); amaximum limit on irradiation time for each sub-volume (voxel) outsidethe target (e.g., for each voxel of normal tissue, treatment time lessthan x2 seconds; x1 and x2 may be the same or different); a minimumlimit on dose rate for each sub-volume (voxel) in the target (e.g., foreach voxel of target tissue, dose rate greater than y1 Gy/sec); and aminimum limit on dose rate for each sub-volume (voxel) outside thetarget (e.g., f or each voxel of normal tissue, dose rate greater thany2 Gy/sec; y1 and y2 may be the same or different). In general, thelimits are intended to minimize the amount of time that normal tissue isirradiated.

FIG. 11 is a flowchart 1100 of an example of computer-implementedoperations for radiation treatment planning in embodiments according tothe present invention. The flowchart 1100 can be implemented ascomputer-executable instructions (e.g., the optimizer model 150 of FIG.3) residing on some form of computer-readable storage medium (e.g.,using the computing system 100 of FIG. 1).

In block 1102 of FIG. 11, values of parameters such as number of beamsto be directed into sub-volumes in a target, directions of the beams,and beam energies are accessed. These parameter values can be generatedusing the system 300 (FIG. 3) and may be stored in a memory of thecomputing system 100 (FIG. 1).

In block 1104 of FIG. 11, information that specifies limits for theradiation treatment plan is accessed. In embodiments, the limits arebased on a dose threshold (see FIGS. 10A and 10B, for example), andinclude a maximum limit on irradiation time for each sub-volume outsidethe target. Other limits can include a maximum limit on irradiation timefor each sub-volume in the target, a minimum limit on dose rate for eachsub-volume in the target, and a minimum limit on dose rate for eachsub-volume outside the target.

In block 1106 of FIG. 11, in embodiments, the values of the parametersare adjusted until the irradiation time for each sub-volume outside thetarget satisfies the maximum limit on irradiation time. In general, thegoal is to minimize the amount of time healthy tissue (tissue outsidethe target) is being irradiated. Note that multiple beams may passthrough a sub-volume outside the target, as long as the totalirradiation time for that sub-volume is less than the limit.

In embodiments, the values of the parameters that affect calculatedamounts of dose to be delivered by the beams are adjusted untilcalculated total doses for the sub-volumes in the target are within aspecified range of each other. In other words, the values of theparameters that affect calculated amounts of dose to be delivered by thebeams are adjusted until calculated total doses for the sub-volumes inthe target are satisfactorily uniform across the entire target.

In block 1112, adjusted parameter values are stored in a memory of thecomputing system 100 (FIG. 1) as part of the radiation treatment plan322 (FIG. 3).

As previously discussed herein, beam directions (gantry angles) aredefined such that the amount of overlap between beam paths is minimizedoutside the target. The goal is have no overlap between beam pathsoutside the target; however, that may not always be possible oradvantageous from the perspective of treating the target.

FIG. 12 is a flowchart 1200 of an example of computer-implementedoperations for radiation treatment planning in embodiments according tothe present invention. The flowchart 1200 can be implemented ascomputer-executable instructions (e.g., the optimizer model 150 of FIG.3) residing on some form of computer-readable storage medium (e.g.,using the computing system 100 of FIG. 1).

In block 1202 of FIG. 12, values of parameters such as number of beamsto be directed into sub-volumes in a target and/or directions of thebeams and beam energies are accessed. These parameter values can begenerated using the system 300 of FIG. 3 and may be stored in a memoryof the computing system 100 of FIG. 1. The beam energies and numberand/or directions of the beams are determined such that the entiretarget receives a minimum prescribed dose.

In block 1204 of FIG. 12, the number of times (how many times) each ofthe beams can be turned on is determined, and the amount of time (howlong) a beam can be turned on each time the beam is turned on is alsodetermined, such that the total amount of time that a beam is turned ondoes not exceed a maximum limit for that beam (e.g., the beam's “ontime” can be minimized).

Note that, as previously mentioned herein, a sub-volume outside thetarget may be irradiated by only one beam, or it may be irradiated bymultiple beams (two or more beams may overlap the sub-volume). Thus, asub-volume outside the target may be irradiated multiple times: thesub-volume may be irradiated multiple times by the same beam (that beamis turned on and off multiple times), or the sub-volume may beirradiated by multiple beams (each of those beams may be turned on andoff once or turned on and off multiple times). However, the total amountof time that a sub-volume can be irradiated is minimized. That is, amaximum limit for irradiation time is specified per sub-volume.Equivalently, a maximum limit on the total amount of time each beam canbe turned on is specified. Thus, the total amount of time each beam isturned on can be minimized while still satisfying the prescribed dose tobe delivered to the target. In this manner, a total amount of time eachsub-volume outside the target is irradiated by the beams does not exceeda maximum limit (e.g., it can be minimized) and, therefore, a totalamount of dose delivered to each sub-volume outside the target does notexceed a maximum limit (e.g., it can be minimized), while stilldelivering the prescribed dose across the entire target.

FIG. 13 is a flowchart 1300 of an example of computer-implementedoperations for calculating doses, in particular a dose calculation foran outside-the-target sub-volume, during radiation treatment planning inembodiments according to the present invention. Significantly, as willbe seen, the methodology of the flowchart 1300 accounts for thetissue-sparing effects of FLASH RT on normal (healthy) tissue. Theflowchart 1300 can be implemented as computer-executable instructions(e.g., the optimizer model 150 of FIG. 3) residing on some form ofcomputer-readable storage medium (e.g., using the computing system 100of FIG. 1).

In block 1302 of FIG. 13, a value for a dose calculation factor for theoutside-the-target sub-volume is accessed. The value for the dosecalculation factor is determined according to how many beams reach theoutside-the-target sub-volume. If a single beam reaches theoutside-the-target sub-volume, then the dose calculation factor has afirst value that is close to zero (e.g., 0.1). If the outside-the-targetsub-volume is reached by more two beams, then the value of the dosecalculation factor is increased (e.g., to 0.3). The dose calculationfactor is increased as the number of beams received by theoutside-the-target sub-volume increases. If the outside-the-targetvolume receives all beams specified in the radiation treatment plan,then the dose calculation factor is 1.0, thus reflecting that thetissue-sparing effects of FLASH RT are not realized.

In block 1304, a dose for the outside-the-target sub-volume iscalculated.

In block 1306, the value of the dose calculation factor is applied tothe dose calculated for the outside-the-target sub-volume. That is, forexample, the calculated dose is multiplied by the dose calculationfactor. If, for example, a single beam is received by the sub-volume,then the calculated dose is reduced by a factor of 0.1, thus recognizingthe tissue-sparing effects of FLASH RT.

In summary, embodiments according to the invention improve radiationtreatment planning and the treatment itself by expanding FLASH RT to awider variety of treatment platforms and target sites. Treatment plansgenerated as described herein are superior for sparing normal tissuefrom radiation in comparison to conventional techniques even fornon-FLASH dose rates by reducing, if not minimizing, the magnitude (andthe integral in some cases) of the dose to normal tissue (outside thetarget) by design. When used with FLASH dose rates, management ofpatient motion is simplified. Treatment planning, while still a complextask of finding a balance between competing and related parameters, issimplified relative to conventional planning. The techniques describedherein may be useful for stereotactic radiosurgery as well asstereotactic body radiotherapy with single or multiple metastases.

In addition to IMRT and IMPT, embodiments according to the invention canbe used in spatially fractionated radiation therapy including high-dosespatially fractionated grid radiation therapy and microbeam radiationtherapy.

Although the subject matter has been described in language specific tostructural features and/or methodological acts, it is to be understoodthat the subject matter defined in the appended claims is notnecessarily limited to the specific features or acts described above.Rather, the specific features and acts described above are disclosed asexample forms of implementing the claims.

What is claimed is:
 1. A computer-implemented method of radiationtreatment planning, the method comprising: accessing values ofparameters from memory of a computing system, wherein the parameterscomprise a number of beams to be directed into sub-volumes in a target,directions of the beams, and beam energies for the beams; accessinginformation that specifies limits for the radiation treatment plan,wherein the limits comprise a maximum limit on irradiation time for eachsub-volume of the sub-volumes in the target; adjusting the values of theparameters until the irradiation time for each sub-volume outside thetarget satisfies the maximum limit on irradiation time; and storing thevalues of the parameters after said adjusting in the memory of thecomputing system as at least a part of the radiation treatment plan. 2.The method of claim 1, wherein each portion of the beams that is in thetarget is represented as a respective set of longitudinal beam regions,and wherein the method further comprises: for each of the beam regions,computing an amount of dose to be delivered by a beam region andassigning a value to the beam region corresponding to the amount; andfor each of the sub-volumes in the target, computing a total value forthe sub-volume by adding together the value for each beam region of eachbeam that reaches the sub-volume; wherein said adjusting furthercomprises adjusting the parameters that affect calculated amounts ofdose to be delivered by the beam regions until differences betweenrespective total values for the sub-volumes in the target satisfy athreshold value.
 3. The method of claim 1, wherein said adjustingfurther comprises: determining whether a beam overlaps any other beamsoutside the target; and weighting beam intensities for beam segments ofthe beam according to how many other beams are overlapped by the beamoutside the target.
 4. The method of claim 1, further comprisingperforming a dose calculation for an outside-the-target sub-volume,wherein said performing a dose calculation comprises: accessing a valuefor a dose calculation factor for the outside-the-target sub-volume,wherein the value for the dose calculation factor is determinedaccording to how many beams reach the outside-the-target sub-volume;calculating a dose for the outside-the-target sub-volume; and applyingthe value of the dose calculation factor to the dose calculated for theoutside-the-target sub-volume.
 5. The method of claim 4, wherein thedose calculation factor reduces the dose calculated for theoutside-the-target sub-volume if only one beam reaches theoutside-the-target sub-volume.
 6. The method of claim 1, wherein thelimits are based on a dose threshold, wherein further the limits areselected from the group consisting of: a maximum limit on irradiationtime for each sub-volume outside the target; a minimum limit on doserate for each sub-volume in the target; and a minimum limit on dose ratefor each sub-volume outside the target.
 7. The method of claim 6,wherein the dose threshold is dependent on tissue type.
 8. The method ofclaim 1, wherein the beams comprise a type of beam selected from thegroup consisting of: proton; electron; photon; atom nuclei; and ion. 9.The method of claim 1, further comprising adjusting the values of theparameters that affect calculated amounts of dose to be delivered by thebeams until calculated total doses for the sub-volumes in the target areeach within a specified range.
 10. A non-transitory computer-readablestorage medium having computer-executable instructions for causing acomputing system to perform a method of generating a radiation treatmentplan, the method comprising: determining a prescribed dose to bedelivered into and across a target; accessing values of parameterscomprising a number of beams in a plurality of beams to be directed intosub-volumes in the target, directions of the plurality of beams, andbeam energies for the plurality of beams, wherein each of the beamscomprises a plurality of beam segments; based on the parameters,identifying any overlapping beams in the plurality of beams that haverespective beam paths that overlap outside the target; for each beam inthe plurality of beams, determining a maximum beam energy for the beamand determining beam energies for the beam segments of the beam as apercentage of the maximum beam energy for the beam; for each overlappingbeam of the overlapping beams that overlap outside the target, reducingplanned beam intensities for the beam segments of the overlapping beamby a factor, wherein the planned beam intensities for the beam segmentsfor the plurality of beams are determined such that a cumulative dosedelivered to the target satisfies the prescribed dose; and storing theplanned beam intensities after said reducing in memory of the computingsystem as at least a part of a radiation treatment plan.
 11. Thenon-transitory computer-readable storage medium of claim 10, wherein themethod further comprises: representing each of the beams in the targetas a respective set of longitudinal beam regions, wherein a valuecorresponding to a calculated amount of dose to be delivered by the beamregion is associated with each beam region in the set; for eachsub-volume in the target, adding together the value for each beam regionof each beam that reaches the sub-volume to determine a total value forthe sub-volume, to produce respective total values for the sub-volumesin the target; and adjusting the values of the parameters that affectthe calculated amounts of dose to be delivered by the beam regions untildifferences between the total values for the sub-volumes satisfy athreshold value.
 12. The non-transitory computer-readable storage mediumof claim 10, wherein the method further comprises: accessing a value fora dose calculation factor for an outside-the-target sub-volume, whereinthe value for the dose calculation factor is determined according to howmany beams reach the outside-the-target sub-volume; calculating a dosefor the outside-the-target sub-volume; and applying the value of thedose calculation factor to the dose calculated for theoutside-the-target sub-volume, wherein the dose calculation factorreduces the dose calculated for the outside-the-target sub-volume ifonly one beam reaches the outside-the-target sub-volume.
 13. Thenon-transitory computer-readable storage medium of claim 10, wherein themethod further comprises using a dose threshold to specify limits forthe radiation treatment plan, wherein the limits are selected from thegroup consisting of: a maximum limit on irradiation time for eachsub-volume in the target; a maximum limit on irradiation time for eachsub-volume outside the target; a minimum limit on dose rate for eachsub-volume in the target; and a minimum limit on dose rate for eachsub-volume outside the target.
 14. The non-transitory computer-readablestorage medium of claim 13, wherein the dose threshold is dependent ontissue type.
 15. The non-transitory computer-readable storage medium ofclaim 10, wherein the beams comprise a type of beam selected from thegroup consisting of: proton; electron; photon; atom nuclei; and ion. 16.A computing system comprising: a central processing unit (CPU); andmemory coupled to the CPU and having stored therein instructions that,when executed by the computing system, cause the computing system toexecute operations to generate a radiation treatment plan, theoperations comprising: accessing, from the memory, values of parameterscomprising a number of beams to be directed into and across a target,directions of the beams, and beam energies for the beams; for each ofthe beams, generating a beam profile of calculated amount of dose versusdepth in the target as a sequence of beam regions; for each beam region,accessing a value that is assigned to the beam region according to acalculated amount of dose to be delivered by the beam region;determining total values for sub-volumes in the target, said determiningcomprising: for each sub-volume in the target, adding together the valuefor each beam region of each of the beams that are received by thesub-volume to determine a total value for the sub-volume; adjusting thevalues of the parameters that affect the beam profile of each of thebeams until the calculated dose inside the target is determined to beuniform across the target as measured by differences between the totalvalues for the sub-volumes; and storing the values of the parametersafter said adjusting in the memory as at least a part of the radiationtreatment plan.
 17. The computing system of claim 16, wherein the beamscomprise a beam comprising a plurality of beam segments, wherein saidadjusting comprises: determining whether the beam overlaps any otherbeams outside the target; and weighting beam intensities for the beamsegments according to how many other beams are overlapped by the beamoutside the target.
 18. The computing system of claim 16, wherein theoperations further comprise performing a dose calculation for anoutside-the-target sub-volume, wherein said performing a dosecalculation comprises: accessing a value for a dose calculation factorfor the outside-the-target sub-volume, wherein the outside-the-targetsub-volume is assigned the value for the dose calculation factoraccording to how many beams are received by the outside-the-targetsub-volume; and calculating a dose for the outside-the-targetsub-volume; and multiplying the dose calculated for theoutside-the-target sub-volume by the value of the dose calculationfactor.
 19. The computing system of claim 18, wherein the dosecalculation factor reduces the dose calculated for theoutside-the-target sub-volume if only one beam reaches theoutside-the-target sub-volume.
 20. The computing system of claim 16,wherein the beams are selected from the group consisting of proton beamsand ion beams and have a respective Bragg peak associated therewith, andwherein, for each beam, the value assigned to the beam regioncorresponding to the Bragg peak of the beam is greater than other valuesassigned to other beam regions.
 21. The computing system of claim 16,wherein the operations further comprise using a tissue-type-dependentdose threshold to specify limits for the radiation treatment plan,wherein the limits are selected from the group consisting of: a maximumlimit on irradiation time for each sub-volume in the target; a maximumlimit on irradiation time for each sub-volume outside the target; aminimum limit on dose rate for each sub-volume in the target; and aminimum limit on dose rate for each sub-volume outside the target.